Exercise treadmill tests in patients with low cardiovascular risk: are we wasting our time?

Transcription

1 Exercise treadmill tests in patients with low cardiovascular risk: are we wasting our time? Sarah Dixon MN; 1 Judy Searle MN; 2 Rachel Forrest PhD; 2 Bob Marshall PhD 2 1 Nelson Marlborough District Health Board, Nelson, New Zealand 2 Eastern Institute of Technology, Napier, New Zealand ABSTRACT INTRODUCTION: The efficacy and cost-effectiveness of exercise treadmill testing for patients with low cardiovascular risk is unclear. This is due to the low incidence of coronary artery disease in this population and the potential for false-positive results leading to additional invasive and expensive investigation. AIM: To investigate the value of exercise treadmill testing (ETT) as a predictor of coronary artery disease in patients with different levels of cardiovascular risk. METHODS: An observational study was completed on an outpatient population from a chest pain clinic (n = 529). Cross-tabulations and binary logistic regressions were used to examine relationships between variables. RESULTS: A negative ETT result was recorded for 72.5% of patients with low cardiovascular risk compared to 54.3% of those with moderate or high risk. Within the low cardiovascular risk group, patients with symptoms atypical for cardiac ischaemia were 11.1-fold more likely to have a negative ETT result. Of the patients with positive or equivocal ETT results, coronary artery disease was subsequently confirmed in only 23.1% of the low cardiovascular risk group compared to 77.2% of those with moderate or high cardiovascular risk. DISCUSSION: Results show low cardiovascular risk patients are significantly more likely to return negative ETT results, particularly when associated with atypical symptoms. Similarly, positive or equivocal ETTs in this group are significantly more likely to be false positives. This suggests the ETT is not efficacious in predicting coronary artery disease in patients with low cardiovascular risk. Is it therefore appropriate to offer exercise testing to this cohort or should alternative management strategies be considered? KEYWORDS: Exercise treadmill test; risk assessment; chest pain; coronary artery disease; retrospective studies J Prim Health Care 2016;8(3): doi: /hc15060 Published online 5 September 2016 CORRESPONDENCE TO: Bob Marshall Health Sciences, Eastern Institute of Technology, PB 1201 Napier, New Zealand bmarshall@eit.ac.nz Introduction Chest pain is a common symptom associated with a variety of diagnoses from the serious to the benign. It often leads to consideration of underlying ischaemic heart disease and it is imperative the possibility of this is effectively assessed. If a resting electrocardiogram (ECG) fails to demonstrate evidence of ischaemia, the exercise treadmill test (ETT) may be used to look for signs of myocardial ischaemia during exertion. There are many other test modalities that can be used (their availability depends on local resources and expertise), but the ETT is perhaps the most cost-efficient, least invasive and readily available method. 1 However, the ETT is not a perfect tool and it is known to give false-positive results, particularly in women and low-risk patients, and 250 CSIRO Publishing Journal Compilation Royal New Zealand College of General Practitioners 2016 This is an open access article licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License

2 false-negative results in higher-risk patients. 2 This makes interpretation challenging, often leading to more invasive and costly tests such as coronary angiography or potentially missing a diagnosis in high-risk patients, as stated in the seminal study by Detry et al. 3 To minimise this risk, it is important to consider both the probability of the disease existing in the individual before the test has been performed and the sensitivity and specificity of the ETT; 67% and 72%, respectively, as reported by Gibbons et al. 1 This will help determine the accuracy of the results. This assessment of pretest probability assists with decisions to proceed with particular diagnostic tests and helps avoid unnecessary testing. Pre-test probability is based on clinician experience, patients presenting symptoms, physical examination and presence of cardiovascular risk factors. 1 In patients presenting with typical symptoms of angina, their pretest probability will most likely be calculated as moderate or high, depending on gender and age and, as a result, the predictive value of the test is increased. Cardiovascular disease (CVD) is the primary cause of mortality in New Zealand and represents 40% of all deaths. 4 The costs related to CVD are of national concern. In the 2011/12 financial year, CVD-related hospitalisations cost the health service NZ$501 million. 5 Coronary artery disease accounted for 57% of these admissions. In the latest review from the National Health Committee, the estimated cost to the health system from coronary artery disease alone was NZ$287 million per annum. 6 Of interest is the recommendation by Fihn et al. who found that diagnostic testing in patients with a >90% or <10% pre-test probability of disease should be discontinued as it adds little to subsequent patient management. 7 Due to increasing fiscal pressures in health care, it is timely to assess these issues. Methods An observational study of data from patients attending a chest pain clinic over an 18-month period was conducted. All patients aged years who completed an ETT using the Bruce protocol for the assessment of stable coronary WHAT GAP THIS FILLS What is already known: The incidence of coronary artery disease is lower in patients with lower cardiovascular risk than in those with moderate or high cardiovascular risk. Exercise treadmill testing (ETT) is a useful tool to rule out obstructive coronary artery disease due to its high negative predictive value. What this study adds: ETT is an ineffective diagnostic test in patients with low cardiovascular risk and atypical symptoms. Any reassurance value of ETT in low cardiovascular risk patients with atypical symptoms is offset by the significant false-positive rate in this group. artery disease were included. 8 Data included cardiovascular risk, gender, whether the patient described typical or atypical symptoms for cardiac ischaemia (as determined by location, character, radiation of pain, trigger for pain, dyspnoea, nausea or diaphoresis), 1 coronary artery disease history, results of the ETT (positive, negative or equivocal), and outcomes of further tests such as coronary angiography. 9 In this clinic, a positive test was based on ST segment depression or elevation of 1 mm (mm) of horizontal or down-sloping ST segment change for ms after the end of the QRS complex and/or provocation of symptoms. A negative ETT meant that no ECG changes or symptoms were provoked with exercise, and in an equivocal result there was some doubt regarding the result due to symptoms or subtle ST changes at high workload. The New Zealand cardiovascular risk assessment was used to risk-stratify all the chest pain clinic patients aged years. 10 Patients aged > 74 years were included because they were considered to have a high cardiovascular risk based purely on age. 10 Patients assessed for reasons other than angina, with known coronary artery disease or with an abnormal resting ECG such as left bundle branch block (which makes interpretation of results difficult) were excluded, as were patients unable to perform an ETT; for example, due to difficulties with mobility. Pearson s Chi-Square test was used to explore the associations between ETT results and gender, cardiovascular risk, and symptom type. For the statistical analysis, cardiovascular risk was VOLUME 8 NUMBER 3 SEPTEMBER 2016 J OURNAL OF PRIMARY HEALTH CARE 251

3 ranked low (< 10%), moderate (10 15%) or high (> 15%). The latter two groups were combined and cross tabulations, odds ratios (OR) and binary logistic regressions were used to explore the following two hypotheses. Hypothesis 1: low cardiovascular-risk patients are significantly more likely to return a negative ETT result than moderate-or high-risk patients. Hypothesis 2: low-risk patients who return a positive or equivocal stress test result are significantly less likely to have coronary artery disease confirmed than moderate- or high-risk patients (i.e. they are more likely to return a false-positive ETT result). Results Data on cardiovascular risk, symptom types (atypical or typical) and ETT result (negative, positive, equivocal) were available for 529 patients, along with their gender and ethnicity. Results of follow-up testing (angiography or stress echo test) were examined for patients with positive or equivocal ETT results (n = 179). Of the 529 patients, 207 were assessed as low cardiovascular risk, of whom 169 (81.6%) were described as having atypical symptoms; 322 patients were categorised as moderate or high cardiovascular risk, with 219 (68%) describing atypical symptoms. Table 1 shows the number of patients within each cardiovascular risk assessment category. There were 204 females (2 Māori) and 325 males (17 Māori) in the sample. Due to the low representation of Māori, ethnicity was not included in the statistical analyses. Table 1. Risk percentages, numbers and New Zealand cardiovascular risk (CVR) category Risk N CVR category* <2.5% <10% 207 Low 10 <15% 164 Moderate 15% 158 High Total 529 * New Zealand Guidelines Group, There were 204 patients with a positive or equivocal result for the ETT and of these, 179 went forward for an angiogram or stress echocardiograph. There were 110 positive results from the angiogram or stress echocardiograph confirming coronary artery disease. Gender was not found to be associated with types of symptoms (P = 0.631) or ETT result (P = 0.328). Level of cardiovascular risk was associated with types of symptoms, with 81.6% of low cardiovascular risk patients having atypical symptoms compared to 68.0% of moderate or high cardiovascular risk patients (P < 0.001, OR = 2.09, 95% CI: ). An association between low cardiovascular risk and negative ETT results was observed, with 72.5% of patients with a low cardiovascular risk having a negative ETT result compared with 54.3% of patients with a moderate or high cardiovascular risk (P < 0.001, OR = 2.21, 95% CI: ). A binary logistic regression, with ETT result (negative or positive/equivocal) as the dependant variable and symptom type and cardiovascular risk as categorical variables, found that the OR of a negative ETT result for type of symptoms (atypical/typical) is (P < 0.001, 95% CI: ) and the OR for cardiovascular risk (low/moderate-high) is 1.85 (P = 0.005, 95% CI: ). Of patients with positive or equivocal ETT results (n = 179), 38.5% recorded a negative result in subsequent investigation to confirm the presence of coronary artery disease (either an angiogram or stress ECG); that is, 38.5% of the ETT results were false positives. A Chi-Square test from further investigation results against cardiovascular risk revealed 76.9% of patients with low cardiovascular risk returned a negative test compared with 22.8% of patients with a moderate or high cardiovascular risk (P < 0.001, OR = 11.26, 95% CI: ). An association also existed between the further investigation result and symptom type, with 53.5% of patients with atypical symptoms returning a negative result compared with 28.7% of 252 VOLUME 8 NUMBER 3 SEPTEMBER 2016 J OURNAL OF PRIMARY HEALTH CARE

4 patients with typical symptoms (P = 0.001, OR = 2.86, 95% CI: ). Similarly, an association existed between further investigation result and gender, with 54.8% of females returning a negative test compared with 27.4% of males with typical symptoms (P < 0.001, OR = 3.22, 95% CI: ). A binary logistic regression, with the follow-up test (angiography or stress echo test) result (negative or positive) as the dependant variable and symptom type and risk as categorical variables, found that the OR of a negative follow-up test for type of symptoms (atypical/typical) was 2.26 (P = 0.025, 95% CI: ) and the OR for cardiovascular risk (low/moderate-high) was (P < 0.001, 95% CI: ). Discussion This study showed that patients with low cardiovascular risk were more likely to have a negative ETT than patients with medium or high cardiovascular risk, supporting hypothesis one. Hypothesis two is also accepted, as patients who did return a positive or equivocal test were less likely to have demonstrable coronary artery disease on subsequent investigation. In other words, there was a significant false-positive rate from ETT in the low-risk group. Negative results: are we wasting our time? In our study, a high number of negative ETT results were found in patients with low cardiovascular risk (72.5%) compared to those with moderate or high cardiovascular risk (54.3%), a result not uncommon in other literature For patients proceeding to coronary angiography or stress echo tests, a negative result was seen in 76.9% of patients with a low cardiovascular risk compared to 22.8% of patients with moderate to high cardiovascular risk, which raises the question as to the value of ETT in this low cardiovascular risk group. Negative test results are reliable in ruling out significant coronary artery disease in patients who complete an adequate ETT (patients with normal resting ECGs and achieving at least 6 min of the Bruce Protocol), and this can be helpful for patients and doctors as it provides reassurance that coronary artery disease is unlikely and allows other causes of symptoms to be pursued. The rate of false positives in our study was 38.5%, a figure comparable to that found for others in acute and stable low-risk patients While considering the risk of a false-positive result, ETTs in this group may lead to more anxiety than they allay. Furthermore, a large number of referrals for low-risk patients with atypical symptoms has contributed to increased waiting time for patients triaged with a greater need. Our study suggests that due to the large numbers of negative- and false-positives test results in the low cardiovascular risk group, ETTs can add little additional information to that attained from thorough clinical assessment. Effectively ruling out cardiac ischaemia in patients with chest pain is a concern for health care providers, particularly those at the first point of contact (primary care or emergency departments), and being able to gain information that patients pain is unlikely to be cardiac related is helpful. Although reassurance is valuable, any testing must be considered in the context of a health care system with increasing demand for health resources but limited ability to meet those demands within reasonable timeframes. 5 Performing ETT for reassurance alone has fiscal implications and puts strain on service provision. Furthermore, ETTs may negatively affect patients by creating unnecessary anxiety and undue stress due to the potential downstream effects of falsepositive results leading to invasive procedures that carry an element of risk. 11,13,17 Atypical symptom presentation In addition to the high negative ETT results in this study, chest pain with features not typical for cardiac ischaemia was more often described in the low cardiovascular risk group compared to patients in the moderate to high cardiovascular risk group (81.6% vs 68%, respectively), a finding consistent with other similar research. 15 Atypical symptoms are frequently described by patients presenting to acute care settings, but ETT is often performed before discharge to exclude VOLUME 8 NUMBER 3 SEPTEMBER 2016 J OURNAL OF PRIMARY HEALTH CARE 253

5 acute coronary syndromes. Negative stress tests also predominate in this group, and results from prognostic testing are similar in patients who describe atypical symptoms whether they present acutely or are referred to an outpatient clinic. 11,14,18,19 This supports the questionable value of ETT in patients with atypical symptoms, particularly if combined with low cardiovascular risk. Recent research suggests it is safe to discharge such patients without ETT. 20 In our study, stable patients were referred primarily from general practice with the benefit of pre-referral assessment to determine patients symptom history, cardiovascular risk and consequent probability of disease. 21 Access thresholds are now an accepted part of many medical services to ensure effective use of public money and protecting services from becoming overburdened. This research suggests a threshold could be reasonably considered to restrict access to ETT to moderate and high cardiovascular risk groups, and low cardiovascular risk patients with symptoms suspicious for ischaemia only. Study limitations This study has inherent weaknesses because randomisation and blinding of diagnostic results was not possible, and the selection of patients may therefore have been biased. Also, there is potential for variations in the classification of symptoms and interpretation of ETT results between different clinicians because two specialist nurses and four cardiologists were involved in the process. However, to standardise data, all clinicians followed the same guidelines and protocols for assessment and interpretation of symptoms and ECG changes. Further, while the study region has a relatively low percentage of Māori (9%), the number of Māori in the data suggests either significant issues of equity of access or problems with the recording of ethnicity in the hospital. Finally, this study was performed in a single location in a regional city of New Zealand and generalisability is difficult to achieve. While reliability and validity enhance the possibility to generalise information from one population to another, it is not possible in this study due to its retrospective design and single-centre location. 22 References 1. Gibbons RJ, Balady GJ, Bricker JT, et al. ACC/AHA 2002 guideline update for exercise testing: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee on exercise testing); [cited 2014 October 20]. Available from: htm 2. Anderson KM, Murphy DL, Balaji M. Essentials of noninvasive cardiac stress testing. J Am Assoc Nurse Pract. 2014;26: doi: / Detry JM, Kapita BM, Cosyns J, et al. Diagnostic value of history and maximal exercise ECG in men and women suspected of coronary artery disease. Circulation. 1977;56: doi: /01.cir Ministry of Health. Diabetes and cardiovascular disease quality improvement plan. Wellington, New Zealand: Ministry of Health; National Health Committee. Strategic overview: cardiovascular disease in New Zealand (working draft). Wellington, New Zealand: National Health Committee; National Health Committee. Ischaemic heart disease (IHD): a pathway to prioritisation. Wellington, New Zealand: National Health Committee; Fihn SD, Gardin JM, Abrahms J, et al. ACCF/AHA/ACP/ AATS/PCNA/SCAI/ STS guideline for the diagnosis and management of patients with stable ischemic heart disease. J Am Coll Cardiol. 2012;60:e doi: /j. jacc Hill J, Timmis A. ABC of clinical electrocardiography. Exercise tolerance testing. BMJ. 2002;324: doi: /bmj Schrock JW, Li M, Orazulike C, Emerman CL. The influence of cardiac risk factor burden on cardiac stress test outcomes. Cardiol Rev. 2011;2: New Zealand Guidelines Group. New Zealand primary care handbook, 3 rd ed. Wellington, New Zealand: New Zealand Guidelines Group; Nawaz Y, Ayub B, Raza M. Stress testing in low risk chest pain patients might not be beneficial. J Sheikh Zayed Med Coll. 2013;4: Arbab-Zadeh A. Stress testing and non-invasive coronary angiography in patients with suspected coronary artery disease: time for a new paradigm. Heart Int. 2012;7:e2. doi: /hi.2012.e2 13. Khare RK, Powell ES, Venkatesh AK, Courtney DM. Diagnostic uncertainty and costs associated with current emergency department evaluation of low risk chest pain. Crit Pathw Cardiol. 2008;7: doi: / HPC.0b013e318176faa1 14. Mazhar J, Killion B, Liang M, et al. Chest pain unit (CPU) in the management of low to intermediate risk acute coronary syndrome: a tertiary hospital experience from New Zealand. Heart Lung Circ. 2012;22: Newman RJ, Darrow M, Cummings DM, et al. Predictive value of exercise stress testing in a family medicine population. J Am Board Fam Med. 2008;21: doi: /jabfm Morise AP. Are the American College of Cardiology/ American Heart Association guidelines for exercise testing for suspected coronary artery disease correct? Chest. 2000;118: doi: /chest Moynihan R, Doust J, Henry D. Preventing overdiagnosis: how to stop harming the healthy. BMJ. 2012;344:e3502. doi: /bmj.e Poldervaart JM, Six AJ, Backus BE, et al. The predictive value of the exercise ECG for major adverse cardiac 254 VOLUME 8 NUMBER 3 SEPTEMBER 2016 J OURNAL OF PRIMARY HEALTH CARE

6 events in patients who presented with chest pain in the emergency department. Clin Res Cardiol. 2013;102: doi: /s Schillinger M, Sodeck G, Meron G, et al. Acute chest pain - identification of patients at low risk for coronary events. The impact of symptoms, medical history and risk factors. Mid Eur J Med. 2004;116: Munro AR, Jerram T, Morton T, Hamilton S. Use of an accelerated diagnostic pathway allows rapid and safe discharge of 70% of chest pain patients from the emergency department. N Z Med J. 2015;128: McConaghy JR, Oza RS. Outpatient diagnosis of acute chest pain in adults. Am Fam Physician. 2013;87: Polit D, Beck C. Nursing research: generating and assessing evidence for nursing practice, 8 th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams Wilkins; ACKNOWLEDGEMENTS The authors would like to acknowledge productive discussions with Dave Dixon, and thank the reviewers for their constructive comments. VOLUME 8 NUMBER 3 SEPTEMBER 2016 J OURNAL OF PRIMARY HEALTH CARE 255